Efficacy, safety and pharmacokinetic profiles of a plasma-derived VWF/FVIII concentrate (VONCENTO®) in subjects with haemophilia A (SWIFT-HA study)

•PK, efficacy and safety of VONCENTO® were investigated in haemophilia A subjects.•VONCENTO® demonstrated bioequivalence to its predecessor.•VONCENTO® provided excellent haemostatic efficacy and was well tolerated.•Annualised bleeding rate significantly lower in prophylaxis than on-demand group•No inhibitory antibodies, TEEs or anaphylactic reactions were identified.

IntroductionVONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate, which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and a VWF/factor VIII (FVIII) ratio of ~ 2.4:1, similar to Haemate® P (CSL Behring).MethodsThe pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre, double-blind, randomised study. Subjects aged ≥ 12 years with haemophilia A who required treatment of non-surgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokinetics were investigated with a single dose of 50 IU FVIII/kg body weight of either VONCENTO® or BIOSTATE® reference product (Biostate-RP) (Day 1; Day 8 [n = 16], repeated on Day 180 [VONCENTO® only; n = 15]). Efficacy and safety analyses were performed either during on-demand treatment (n = 52) or prophylaxis (n = 29) for ≥ 6 months and ≥ 50 exposure days, respectively.ResultsBesides the confirmation of bioequivalence between VONCENTO® and Biostate-RP, which displayed comparable PK profiles, haemostatic efficacy was rated by the investigators as either 'excellent' or 'good' in 96.4% of all bleeding events (96.5% spontaneous, 96.6% traumatic, 96.9% joint bleeds) as well as in 80% of major and 100% of minor surgical procedures at discharge. The median number of annualised bleeding events per subject [range] was significantly lower in the prophylaxis group (2.0 [0.0-34.6]) than in the on-demand group (14.0 [0.0-87.8], p = 0.0013).VONCENTO® was well tolerated and no inhibitory antibodies were identified during the study period.ConclusionsThis study demonstrated the bioequivalence of VONCENTO® to Biostate-RP, and its excellent efficacy and safety profile in haemophilia A subjects.